Flucytosine (Monograph)

Brand name: Ancobon
Drug class: Pyrimidines

Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP.

Introduction

Antifungal; fluorinated pyrimidine analog.^{120 180}

Uses for Flucytosine

Candida Infections

Treatment of serious Candida infections, including urinary tract or pulmonary infections, candidemia, endocarditis, meningitis, and endophthalmitis.^{120 133 146 167 425} Usually used in conjunction with IV amphotericin B.^{120 133 146 167 425} Should not be used alone for systemic candidiasis or severe, life-threatening infections since it may be ineffective or result in emergence of flucytosine resistance.^{120 167 425}

For treatment of CNS candidiasis in adults, IDSA recommends initial treatment with IV amphotericin B (with or without oral flucytosine) followed by step-down treatment with fluconazole.⁴²⁵

Although oral flucytosine has been used in conjunction with IV amphotericin B for treatment of severe invasive candidiasis, including CNS candidiasis, in pediatric patients^{† [off-label]},⁴⁴¹ this regimen not usually recommended for treatment of candidiasis in children, including HIV-infected children.⁴⁴¹ AAP and others state that routine use of flucytosine for treatment of meningitis in neonates^{† [off-label]} not recommended because of toxicity concerns.^{292 441} IDSA states consider salvage therapy with a regimen of flucytosine and amphotericin B in neonates^{† [off-label]} only if there is no response to amphotericin B alone.⁴²⁵

For treatment of endocarditis (native or prosthetic valve) or implantable cardiac device infections caused by Candida, IDSA recommends initial treatment with a lipid formulation of IV amphotericin B (with or without oral flucytosine) or an IV echinocandin (anidulafungin, caspofungin, micafungin) followed by step-down treatment with fluconazole.⁴²⁵

For treatment of urinary tract infections caused by Candida, especially fluconazole-resistant strains, oral flucytosine is used alone or in conjunction with IV amphotericin B.⁴²⁵ IDSA states antifungal treatment not usually indicated in patients with asymptomatic cystitis, unless there is high risk of disseminated candidiasis (e.g., neutropenic patients, low-birthweight infants [<1.5 kg], patients undergoing urologic manipulations).⁴²⁵ Fluconazole is drug of choice for treatment of symptomatic cystitis, pyelonephritis, or fungus balls likely to be caused by fluconazole-susceptible Candida.⁴²⁵ When fluconazole-resistant C. glabrata are likely, IV amphotericin B or oral flucytosine recommended for symptomatic cystitis and IV amphotericin B (with or without oral flucytosine) or oral flucytosine alone recommended for pyelonephritis.⁴²⁵

For treatment of endophthalmitis caused by fluconazole- and voriconazole-resistant Candida in adults, IDSA states IV amphotericin B liposomal (with or without oral flucytosine) is regimen of choice.⁴²⁵ Decisions regarding antifungal treatment and surgical intervention should be made jointly by an ophthalmologist and infectious disease clinician.⁴²⁵

Cryptococcosis

Treatment of serious cryptococcal infections, including pulmonary infections, septicemia, and meningitis, caused by Cryptococcus neoformans.^{109 110 111 112 113 115 116 119 120 128 133 145 147 167 292 427 436 440 441} Should not be used alone for treatment of cryptococcosis.^{120 427 436 440 441}

Usually used in conjunction with IV amphotericin B for initial treatment of cryptococcal infections, especially cryptococcal meningitis in HIV-infected patients.^{128 134 135 145 167 292 427 436 440 441} Addition of flucytosine to the amphotericin B regimen for initial treatment may reduce the time required for sterilization of CSF in those with CNS involvement.^{107 110 111 116 118 427 440} Has also been used in conjunction with fluconazole for treatment of cryptococcal meningitis in HIV-infected individuals.^{292 427 440 441}

For treatment of cryptococcal meningitis in HIV-infected adults, adolescents, and children, CDC, NIH, IDSA, and others state that the preferred regimen is initial (induction) therapy with IV amphotericin B (liposomal or conventional formulation) given in conjunction with oral flucytosine for at least 2 weeks until there is evidence of clinical improvement and negative CSF cultures after repeat lumbar puncture, then follow-up (consolidation) therapy with oral or IV fluconazole given for at least 8 weeks, followed by long-term suppressive or maintenance therapy (secondary prophylaxis) with oral fluconazole to complete ≥1 year of azole therapy.^{427 436 440 441}

One alternative regimen for initial (induction) treatment of cryptococcal meningitis in HIV-infected adults, adolescents, and children who cannot receive the preferred regimen is oral or IV fluconazole used in conjunction with oral flucytosine.^{292 427 440 441} Alternative regimens may be less effective and are recommended only in patients who cannot tolerate or have not responded to the preferred regimen.^{427 440 441}

Although data are limited, CDC, NIH, and IDSA state that recommendations for treatment of CNS, pulmonary, or disseminated infections caused by C. gattii and recommendations for long-term suppressive or maintenance therapy (secondary prophylaxis) of C. gattii infections are the same as recommendations for C. neoformans infections.^{427 440} IDSA states that single, small cryptococcoma may be treated with oral fluconazole, but induction therapy with a regimen of conventional IV amphotericin B and oral flucytosine given for 4–6 weeks, followed by consolidation therapy with fluconazole given for 6–18 months should be considered for very large or multiple cryptococcomas caused by C. gattii.⁴²⁷ Regimens that include IV amphotericin B (conventional or liposomal formulation), flucytosine, and fluconazole have been effective in a few patients with CNS infections known to be caused by C. gattii.^{163 164 165}

Chromoblastomycosis

Treatment of chromoblastomycosis^{† [off-label]} (chromomycosis) caused by various dematiaceous fungi (e.g., Cladosporium, Exophiala, Phialophora).^{133 138 139 143 161 167 179 180}

Optimum regimens for chromoblastomycosis not identified.^{133 138 143 179} Azole antifungals (usually itraconazole) or terbinafine have been effective and may be the preferred antifungals for treatment of chromoblastomycosis;^{179 133} surgery and/or adjunctive use of other therapies (e.g., heat therapy, laser therapy, photodynamic therapy) may be indicated.^{179 133}

Regimen of itraconazole and flucytosine has been effective in some patients;^{139 179} regimen of posaconazole and flucytosine suggested as a possible alternative in refractory cases.¹⁷⁹ Regimen of amphotericin B and flucytosine no longer recommended for such infections.¹⁷⁹

Aspergillosis

Has been used in conjunction with IV amphotericin B for treatment of invasive aspergillosis^{† [off-label]} or other infections caused by Aspergillus (e.g., osteomyelitis and joint infections).^{133 137 148 160 167} Unclear whether concomitant amphotericin B and flucytosine offers any benefit over amphotericin B alone for treatment of invasive aspergillosis,^{133 167} and there are concerns related to possible increased risk of adverse effects.^{137 160}

Voriconazole is considered drug of choice for initial treatment of invasive aspergillosis in most patients; IV amphotericin B (a lipid formulation) is preferred alternative.^{423 436}

Free-living Ameba Infections

Has been used in conjunction with other anti-infectives in a few patients for treatment of free-living ameba infections^†, including granulomatous amebic encephalitis or other infections caused by Acanthamoeba^{†134 173 174 175 190} or Balamuthia mandrillaris^†.^{134 176 177 190}

CNS infections caused by free-living ameba have high mortality rate,^{134 171 172 173 190} and only very limited number of cases have been successfully treated.^{172 173 190} Early diagnosis and treatment with a multiple-drug regimen may increase chance of survival.^{172 292}

Although data are limited, most reported cases of Acanthamoeba and B. mandrillaris infection have been treated empirically with regimens that include a variety of anti-infectives (e.g., albendazole, amphotericin B, azole antifungals [fluconazole, itraconazole, ketoconazole], flucytosine, macrolides [azithromycin or clarithromycin], miltefosine, rifampin, pentamidine, sulfonamides [co-trimoxazole or sulfadiazine]).^{134 172 173 174 175 176 177 292 190}

Contact CDC Emergency Operations Center at 770-488-7100 for assistance with diagnosis or treatment of suspected free-living ameba infections.^{171 172}

Flucytosine Dosage and Administration

Administration

Oral Administration

Administer orally.¹²⁰ Nausea or vomiting may be reduced or avoided if each dose is administered by ingesting a few capsules at a time over a 15-minute period.¹²⁰

Extemporaneously Compounded Oral Suspension

For patients unable to swallow capsules, oral suspensions containing 10 or 50 mg/mL have been prepared extemporaneously using the commercially available capsules.^{186 187 188}

Standardize 4 Safety

Standardized concentrations for an extemporaneously prepared oral suspension of flucytosine have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care.²⁵² Because recommendations from the S4S panels may differ from the manufacturer’s prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label. For additional information on S4S (including updates that may be available), see [Web].²⁵²

Dosage

Prolonged serum flucytosine concentrations >100 mcg/mL may be associated with increased risk of toxicity (e.g., adverse hematologic, GI, and hepatic effects).^{120 150 169 170} Adjust dosage to ensure that serum concentrations remain <100 mcg/mL.^{133 150 169 170 436} Optimal target serum concentrations not identified,¹⁷⁰ and a variety of target ranges have been recommended.^{150 167 168 169 170 292 427 440 441}

AAP, CDC, NIH, IDSA, and others generally recommend target serum concentrations of 30–80 mcg/mL.^{150 292 427 440 441}

Some clinicians suggest measuring serum flucytosine concentrations beginning 3–5 days after initiation of the drug⁴²⁷ (or beginning after 3–5 doses)⁴⁴⁰ and then once or twice weekly during treatment^{133 425} and whenever there is evidence of toxicity or a change in renal function.¹⁶⁸ Peak serum concentrations usually measured using blood samples taken 2 hours after an oral dose.^{292 427 440}

Pediatric Patients

General Pediatric Dosage†

Oral

100 mg/kg daily given in 4 divided doses every 6 hours recommended by AAP.²⁹²

Candida Infections

CNS Candidiasis

Oral

Neonates^†: If salvage therapy indicated because of nonresponse to initial treatment with IV amphotericin B alone, IDSA states consider adding flucytosine 25 mg/kg 4 times daily to the amphotericin B regimen.⁴²⁵ After several weeks and when response attained, transition to fluconazole step-down therapy.⁴²⁵ Continue antifungal treatment until all signs, symptoms, CSF abnormalities, and radiologic abnormalities (if present) have resolved.⁴²⁵

Cryptococcosis

Oral

Children with CNS or disseminated cryptococcosis^†: Induction therapy with 100 mg/kg daily in 4 divided doses in conjunction with IV amphotericin B for at least 2 weeks, then consolidation therapy with oral fluconazole alone for at least 8 weeks.⁴²⁷

HIV-infected infants, children, and adolescents with cryptococcal meningitis^†: Induction therapy with 25 mg/kg 4 times daily in conjunction with IV amphotericin B for at least 2 weeks until there is evidence of clinical improvement and negative CSF cultures after repeat lumbar puncture, then consolidation therapy with oral or IV fluconazole alone.^{427 441}

HIV-infected infants and children with cryptococcal meningitis who cannot receive amphotericin B^†: Induction therapy with 25 mg/kg 4 times daily in conjunction with oral or IV fluconazole.⁴⁴¹

HIV-infected infants and children with severe pulmonary or disseminated (non-CNS) cryptococcosis^†: 25 mg/kg 4 times daily in conjunction with IV amphotericin B.⁴⁴¹ Treatment duration depends on response and site and severity of infection.⁴⁴¹

Adults

General Adult Dosage

Oral

Manufacturer recommends 50–150 mg/kg daily given in 4 divided doses at 6-hour intervals.¹²⁰ In patients with elevated BUN or S_cr, use lower dosage initially.¹²⁰

To reduce risk of toxicity when used in conjunction with IV amphotericin B, some clinicians suggest a low initial dosage (i.e., 75 mg/kg daily given in 4 divided doses).⁴³⁶ Dosage can then be adjusted based on serum flucytosine concentrations and presence or absence of amphotericin B-associated renal toxicity.⁴³⁶

Candida Infections

CNS Candidiasis

Oral

25 mg/kg 4 times daily in conjunction with IV amphotericin B for several weeks, then follow-up therapy with fluconazole alone.⁴²⁵ Continue antifungal treatment until signs and symptoms, CSF abnormalities, and radiologic abnormalities resolve.⁴²⁵

Candida Cardiovascular Infections

IV

25 mg/kg 4 times daily in conjunction with IV amphotericin B.⁴²⁵ If infection caused by fluconazole-susceptible Candida, consider transitioning to oral fluconazole after patient stabilized and Candida cleared from bloodstream.⁴²⁵

Symptomatic Cystitis, Pyelonephritis, or Fungus Balls

Oral

Symptomatic cystitis caused by fluconazole-resistant C. glabrata: 25 mg/kg 4 times daily for 7–10 days.⁴²⁵

Pyelonephritis caused by fluconazole-resistant C. glabrata: 25 mg/kg 4 times daily in conjunction with IV amphotericin B for up to 7 days.⁴²⁵ If used without IV amphotericin B, 25 mg/kg 4 times daily for 2 weeks recommended.⁴²⁵

Fungus balls: 25 mg/kg 4 times daily in conjunction with IV amphotericin B for up to 7 days.⁴²⁵ If used without IV amphotericin B, 25 mg/kg 4 times daily for 2 weeks recommended.⁴²⁵

Candida Endophthalmitis

Oral

Endophthalmitis caused by fluconazole- and voriconazole-resistant Candida: 25 mg/kg 4 times daily in conjunction with IV amphotericin B liposomal.⁴²⁵ Duration of treatment is at least 4–6 weeks as determined by repeated examinations to verify resolution.⁴²⁵

Cryptococcosis

Oral

Severe cryptococcal infections: 100–150 mg/kg daily in conjunction with another antifungal (e.g., IV amphotericin B, fluconazole).^{128 132 135 145 436}

HIV-infected adults with cryptococcal meningitis: Induction therapy with 25 mg/kg 4 times daily in conjunction with IV amphotericin B given for at least 2 weeks until there is evidence of clinical improvement and negative CSF cultures after repeat lumbar puncture, then consolidation therapy with oral or IV fluconazole alone.^{427 440}

HIV-infected adults with cryptococcal meningitis who cannot receive amphotericin B: Induction therapy with 25 mg/kg 4 times daily in conjunction with oral or IV fluconazole.^{427 440}

Free-living Ameba Infections†

Oral

Granulomatous amebic encephalitis or other infections caused by Acanthamoeba^† or Balamuthia mandrillaris^†: Some clinicians recommend 37.5 mg/kg every 6 hours (up to 150 mg/kg daily);¹³⁴ higher dosage has been used in some patients.^{176 177} Use in conjunction with other anti-infectives.^{134 173 174 175 176 177} (See Free-living Ameba Infections under Uses.)

Special Populations

Renal Impairment

Use with extreme caution¹²⁰ and reduce dosage.^{120 133 180 425 427 440}

Several methods proposed for calculating flucytosine dosage for patients with impaired renal function.^a For greater accuracy, base dosage on actual serum flucytosine concentrations.⁴⁴⁰ Precise dosing is limited since flucytosine is commercially available only as 250- and 500-mg capsules.^a

Some clinicians recommend 25 mg/kg every 12 hours in adults with Cl_cr of 20–40 mL/minute, 25 mg/kg once daily in those with Cl_cr of 10–20 mL/minute, and 25 mg/kg once every 48 hours in those with Cl_cr <10 mL/minute.⁴⁴⁰

Others state that usual individual dose (12.5–37.5 mg/kg) can be administered every 12 hours in patients with Cl_cr 20–40 mL/minute, every 24 hours in those with Cl_cr 10–20 mL/minute, and every 24–48 hours or longer (as determined by serum drug concentrations) in those with Cl_cr <10 mL/minute.^a

Alternatively, other clinicians recommend that doses of 12–35 mg/kg be given at intervals equal to twice the half-life of the drug.^a

In patients undergoing hemodialysis, some clinicians recommend that doses of 20–50 mg/kg be given every 48–72 hours and that doses be administered after dialysis.⁴⁴⁰

Geriatric Patients

Select dosage with caution because of age-related decreases in renal function; adjust dosage based on renal function.¹⁸⁰

Cautions for Flucytosine

Contraindications

• Hypersensitivity to flucytosine.¹²⁰

Warnings/Precautions

Warnings

Hematologic Effects

Anemia,¹²⁰ leukopenia,¹²⁰ pancytopenia,¹²⁰ thrombocytopenia,¹²⁰ eosinophilia,¹²⁰ agranulocytosis,¹²⁰ and aplastic anemia¹²⁰ reported.

Fatal bone marrow aplasia reported in some patients.¹²⁰ Bone marrow toxicity can be irreversible and may be fatal in immunosuppressed patients.¹²⁰

Risk of bone marrow toxicity is increased in patients who have hematologic disease and in those who are receiving or previously received radiation or drug therapy that depresses the bone marrow.¹²⁰ Risk of adverse hematologic effects also may be increased in patients who have prolonged, high serum flucytosine concentrations (i.e., >100 mcg/mL),¹²⁰ particularly in those with renal dysfunction or during concomitant therapy with amphotericin B.^a

Use with extreme caution in patients with bone marrow depression.¹²⁰

Monitor hematologic function frequently during therapy.¹²⁰ (See Laboratory Monitoring under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Rash,¹²⁰ pruritus,¹²⁰ urticaria,¹²⁰ toxic epidermal necrolysis (Lyell syndrome),¹²⁰ and photosensitivity¹²⁰ reported.

Anaphylaxis reported rarely.^{103 120}

General Precautions

Laboratory Monitoring

Hematologic, renal, and hepatic status must be monitored closely during flucytosine therapy.¹²⁰

Prior to initiation of therapy, determine hematologic status (leucocyte and thrombocyte count), renal function, hepatic function (serum alkaline phosphatase, AST, ALT), and serum electrolytes (hypokalemia).¹²⁰

During therapy, frequently monitor hematologic, renal, and hepatic function.¹²⁰

Monitor serum flucytosine concentrations to minimize risk of toxicity, especially in patients with renal impairment.^{133 150 169 170 436} (See Dosage under Dosage and Administration.)

Specific Populations

Pregnancy

Teratogenic in rats.¹²⁰ When given to pregnant rats in a dosage of 0.051 times the human dosage, vertebral fusions occurred;¹²⁰ at a dosage of 0.89 times the human dosage, cleft lip and palate and micrognathia reported.¹²⁰

No adequate or controlled studies to date using flucytosine in pregnant women.¹²⁰

Use during pregnancy only when potential benefits justify possible risks to the fetus.^{118 120 440}

Lactation

Not know whether distributed into human milk.¹²⁰

Discontinue nursing or the drug, taking into account the importance of the drug to the mother.¹²⁰

Pediatric Use

Safety and efficacy not systematically studied in children.¹²⁰

If used in neonates and infants^†, closely monitor serum concentrations of the drug.^{120 180 425} Limited data regarding flucytosine pharmacokinetics in neonates indicate considerable interindividual variation in plasma concentrations attained.^{120 191} High plasma concentrations of the drug may accumulate in very low-birthweight infants because of immature renal function.⁴²⁵

Some clinicians state avoid flucytosine in children^† with severe renal impairment.⁴⁴¹

Has been used in some neonates^† (with or without concomitant amphotericin B) without unusual adverse effects.¹²⁰ Hypokalemia, acidemia, anemia, and thrombocytopenia have been reported.¹²⁰

Geriatric Use

Dosage adjustment may be required in geriatric patients based on renal function.¹⁸⁰ (See Renal Impairment under Dosage and Administration.)

Hepatic Impairment

Pharmacokinetics not affected by hepatic impairment.¹³³

Renal Impairment

Use with extreme caution in patients with impaired renal function.¹²⁰

Eliminated mainly by the kidneys; renal impairment may lead to drug accumulation and increased risk of toxicity.¹²⁰

Adjust dosage in patients with renal impairment.¹²⁰ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Bone marrow suppression; GI effects (anorexia, abdominal bloating or pain, diarrhea, dry mouth, duodenal ulcer, GI hemorrhage, nausea, vomiting, ulcerative colitis, enterocolitis); hepatic effects; renal effects; CNS effects (confusion, hallucinations, psychosis).^{120 167 a}

Drug Interactions

Specific Drugs

Flucytosine Pharmacokinetics

Absorption

Bioavailability

Rapidly and almost completely absorbed from GI tract;¹²⁰ bioavailability is 78–90%.^{120 180}

In normal renal function, peak serum flucytosine concentrations reached within 2 hours following a single 2-g oral dose.¹²⁰

Food

Food decreases rate, but not extent, of absorption.^a

Special Populations

In a limited number of neonates receiving oral flucytosine, mean time to peak serum concentrations was 2.5 hours after a dose.¹²⁰ Considerable interindividual variation in serum concentrations that is not correlated with gestational age.¹²⁰

Peak serum concentrations are higher, more prolonged, and reached more slowly in patients with impaired renal function.^a

In anephric patients, peak serum concentrations may be 50% higher than in patients with normal renal function.^a

Distribution

Extent

Widely distributed into body tissues and fluids including liver, kidney, spleen, heart, bronchial secretions,¹³³ joints,¹³³ peritoneal fluid,¹³³ brain,¹³³ bile,¹³³ bone,¹³³ and aqueous humor.¹³³

Distributed into CSF;¹²⁰ concentrations in CSF may be 60–100% of serum concentrations.^a

Crosses placenta after intraperitoneal administration in pregnant rats.¹²⁰

Not known whether distributed into milk.^a

Plasma Protein Binding

2.9–4% bound to serum proteins.¹²⁰

Elimination

Metabolism

Only minimal amounts are metabolized.^a Deaminated (probably by gut bacteria) to fluorouracil.¹²⁰ AUC ratio of fluorouracil to flucytosine is 4%.¹²⁰

Elimination Route

Eliminated by kidneys, principally by glomerular filtration without substantial tubular reabsorption.¹²⁰ Unabsorbed flucytosine excreted unchanged in feces.¹⁸⁰

>90% of an oral dose excreted unchanged in urine.¹²⁰

Removed by peritoneal dialysis.¹³³

Removed by hemodialysis.^{120 133}

Half-life

2.4–4.8 hours in normal renal function.¹²⁰

Special Populations

In a limited number of neonates and infants^†, median half-life was 7.4 hours.^{120 191}

Half-life prolonged in renal impairment.^a

Half-life is 6–14 hours in those with Cl_cr 40 mL/minute, 12–15 hours in those with Cl_cr 20 mL/minute, 21–27 hours in those with Cl_cr 10 mL/minute, and 30–250 hours in those with Cl_cr <10 mL/minute.^a Half-lives up to 1160 hours have been reported when Cl_cr <2 mL/minute.^a

Stability

Storage

Oral

Capsules

25°C; may be exposed to 15–30°C.¹²⁰

Actions and Spectrum

• Fluorinated pyrimidine antifungal.^{120 180}

• May be fungistatic or fungicidal in action, depending on concentration of the drug.¹⁵¹

• Appears to enter fungal cells via the action of fungal-specific cytosine permease.^{120 150 167} Inside the cell, flucytosine is converted into fluorouracil (5-FU) by cytosine deaminase and then converted into 5-fluorouridine triphosphate (FUTP).^{150 151 167} FUTP is incorporated into fungal RNA and interferes with protein synthesis.^{150 151 167}

• Flucytosine also appears to be converted to 5-fluorodeoxyuridine monophosphate, which noncompetitively inhibits thymidylate synthetase and interferes with DNA synthesis.^{150 151 167}

• Does not appear to have antineoplastic activity.^a

• Candida: Active in vitro and in clinical infections¹²⁰ against C. albicans.^{120 152 162 180 189} Also active in vitro against C. glabrata,^{152 162 180 189} C. guilliermondii,^{162 180} C. parapsilosis,^{152 162 180 189} and C. tropicalis.^{152 162 180 189} Some strains of C. krusei^{162 180} and C. lusitaniae¹⁶² may be susceptible, but others are resistant.^{154 155 180} Some clinical isolates of C. auris (often misidentified as C. haemulonii, C. famata, or Rhodotorula glutinis) have been susceptible to flucytosine in vitro; however, wide range of MICs reported and reduced susceptibility or resistance to flucytosine occurs.^{184 185} C. kefyr usually resistant.¹⁶²

• Cryptococcus: Active in vitro and in clinical infections¹²⁰ against C. neoformans.^{120 152 153 180} Also active in vitro against C. gattii.^{158 162}

• Causative agents of chromoblastomycosis and phaeohyphomycosis: Some in vitro evidence of activity against some strains of Cladophialophora,^{180 182 183} Phialophora verrucosa,^{178 180} Exophiala (E. castellanii, E. dermatitidis, E. spinifera),^{143 180} and Cladosporium.¹⁸⁰ Although some strains of Fonsecaea are susceptible in vitro,¹⁸⁰ flucytosine reportedly has limited or no activity against this organism.^{179 181}

• Other fungi: Has some in vitro activity against Aspergillus^a and Sporothrix schenckii,^a but these fungi generally considered resistant to flucytosine.¹⁸⁰ Inactive against Blastomyces dermatitidis,¹⁸⁰ Coccidioides immitis,¹⁸⁰ Histoplasma capsulatum,¹⁸⁰ Paracoccidioides brasiliensis,¹⁸⁰ Madurella,¹⁸⁰ dermatophytes (Microsporum, Trichophyton, Epidermophyton),¹⁸⁰ and bacteria.¹⁸⁰

• Resistance to flucytosine can be readily induced in vitro in Candida and C. neoformans.¹⁸⁰ Resistant strains of Candida and C. neoformans have emerged in patients receiving oral flucytosine alone^{120 137 150 151 180} or in conjunction with IV amphotericin B.^{137 150 151 180}

• No cross-resistance between flucytosine and amphotericin B.¹²⁰

Advice to Patients

• Advise patients that incidence and severity of nausea or vomiting may be decreased or eliminated if each dose is administered by ingesting the capsules a few at a time over a 15-minute period.¹²⁰

• Importance of informing clinician of existing or contemplated therapy, including prescription and OTC drugs, or any concomitant illness.¹²⁰

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹²⁰

• Importance of advising patients of other important precautionary information.¹²⁰ (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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